Experimental evidences and signal transduction pathways involved in the activation of NF-κB/Rel by angelan in murine macrophages

In our previous studies, we showed that angelan, a polysaccharide purified from Angelica gigas Nakai, activated macrophages to induce the translocation of NF-κB/Rel into nucleus and DNA binding to its cognate site in the promoter of iNOS gene [Immunopharmacology 43 (1999) 1; Immunopharmacology 49 (2000) 275]. In the present study, we showed that angelan induces the transcriptional activation of NF-κB/Rel and investigated the intracellular signal transduction pathways involved in the angelan-induced NF-κB/Rel activation by murine macrophages. Treament of RAW 264.7 cells with angelan resulted in significant activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and p38, while stress-activated protein kinase/c-Jun NH2 terminal kinase (SAPK/JNK) was not activated by angelan. The specific p38 inhibitor SB203580 abrogated the angelan-induced NF-κB/Rel activation, whereas the selective MAPK/extracellular signal-regulated kinase 1 (MEK-1) inhibitor PD98059 did not affect the NF-κB/Rel induction. Treatment of RAW 264.7 cells with both anti-CD14 Ab and anti-CR3 Ab significantly blocked angelan-induced NF-κB/Rel activation. In conclusion, we demonstrate that angelan induces NF-κB/Rel activation through the CD14 and CR3 membrane receptor and p38 kinase that is critically involved in the signal transduction leading to NF-κB/Rel activation in murine macrophages.